ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.4897G>A (p.Asp1633Asn)

dbSNP: rs1555740805
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000518921 SCV000618426 pathogenic not provided 2023-02-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31785789, 29165669, 19344873, 33798445, 34445196)
Ambry Genetics RCV000624265 SCV000742698 uncertain significance Inborn genetic diseases 2017-07-17 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001095766 SCV001251609 likely pathogenic CACNA1A-related disorders 2020-01-24 criteria provided, single submitter clinical testing The CACNA1A c.4900G>A (p.Asp1634Asn) variant is a missense variant. It is reported as a de novo variant, though without confirmed parentage, in one individual in the DECIPHER database (Firth et al. 2009, patient 259278). The reported phenotype of this individual is consistent with CACNA1A-related disorders and includes global developmental delay, intellectual disability, sleep disturbance, unsteady gait, falls, behavioral abnormalities, brachycephaly, strabismus, and bilateral single transverse palmar creases. The p.Asp1634Asn variant has also been identified by clinical laboratories in individuals with neurodevelopmental phenotypes consistent with CACNA1A-related disorders and submitted to the ClinVar database (Landrum et al. 2018); however these cases are not reported in the published literature and clinical details are limited. This variant is not found in the Genome Aggregation Database in a region of good sequencing coverage, so the variant is presumed to be rare. The p.Asp1634Asn variant occurs at a conserved residue in the S3 transmembrane segment of domain IV of the voltage-dependent P/Q-type calcium channel subunit alpha-1A protein, though the function of this region is unknown. In silico predictions suggest a damaging consequence, however this has not been evaluated experimentally. Based on the collective evidence and the application of ACMG criteria, the p.Asp1634Asn variant is classified as likely pathogenic for CACNA1A-related disorders.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris RCV001644622 SCV001519108 pathogenic Episodic ataxia type 2 2021-01-04 criteria provided, single submitter research
Wendy Chung Laboratory, Columbia University Medical Center RCV002227176 SCV002506524 likely pathogenic Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 52 2022-03-20 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.